Adiponectin Mediated MHC Class II Mismatched Cardiac Graft Rejection in Mice Is IL-4 Dependent 英文参考文献.docVIP
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Adiponectin Mediated MHC Class II Mismatched Cardiac Graft Rejection in Mice Is IL-4 Dependent 英文参考文献
AdiponectinMediatedMHCClassIIMismatchedCardiac
GraftRejectioninMiceIsIL-4Dependent
DaxuLi1¤,JuliaY.S.Tsang1,JiaoPeng1,DerekH.H.Ho2,YeeKwanChan3,JiangZhu1,VincentC.H.Lui1,
AiminXu4,JonathanR.Lamb5,PaulK.H.Tam1*,YanChen1,2*
1PaediatricSurgeryDivision,DepartmentofSurgery,TheUniversityofHongKong,HongKongSAR,China,2DepartmentofChemistry,TheUniversityofHongKong,
HongKongSAR,China,3SchoolofBiologicalScience,TheUniversityofHongKong,HongKongSAR,China,4DepartmentofMedicine,TheUniversityofHongKong,
HongKongSAR,China,5DivisionofCellandMolecularBiology,FacultyofNaturalSciences,ImperialCollegeLondon,London,UnitedKingdom
Abstract
Background:Adiponectinregulatesglucoseandfatty-acidmetabolismbutitsroleinchronicgraftrejectionmediatedby
Th2cytokinesremainsill-defined.
Methodology/PrincipalFindings:Wildtypeandadiponectin-nullmicewereusedasgraftrecipientsinmouseMHCclassII
disparatecardiactransplantation(bm12toB6)andthegraftrejectionwasmonitored.Inadiponectin-nullmiceweobserved
+
+
that the cellular infiltrate of eosinophils, CD4 and CD8 T cells was reduced in grafts compared to the controls as was
collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil
infiltrationwasincreased.LowlevelsofIL-4weredetectedinthegraftsandserum.TheeffectofadiponectinsignalingonIL-
4expressionwasfurtherinvestigated.TreatmentwithAMPKandp38MAPKinhibitorsblockedadiponectinenhancedTcell
proliferationinmixedlymphocytereactions.InhibitionofAMPKreducedeosinophilinfiltrationinskingraftsinwildtype
recipientsandincontrastAMPKactivationincreasedeosinophilsinadiponectin-nullrecipients.Theadditionofadiponectin
increasedIL-4productionbytheTcelllineEL4withaugmentednuclearGATA-3andphospho-STAT6expressionwhichwere
suppressedbyknockdownofadiponectinreceptor1and2.
Conclusions:OurresultsdemonstrateadirecteffectofadiponectinonIL-4expressionwhichcontributestoTh2cytokine
mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our und
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